1. Field of the Invention
The present invention generally relates to antibody plus (A+) biomarker assays for detecting and diagnosing cancer in subjects.
2. Description of the Related Art
Molecular identification of tumor-associated antigens (TAAs) has clearly demonstrated that the human immune system can react with endogenously arising cancer cells. See van der Bruggen et al. (1991) Science 254:1643-7. Both the cellular and humoral arms of the human immune system recognize TAA derived from cancer cells. See Rosenberg S A (2001) Nature 411:380-4; and Old et al. (1998) J Exp Med 187:1163-7. Of particular interest to the serological analysis of human cancers is the identification of TAA recognized by antibodies (Ab) present in the sera of cancer patients. See Sahin et al. (1997) Curr Opin Immunol 9:709-16. Ab-defined TAA provide molecular details of the humoral immune response to autologous tumors.
To investigate Ab responses that cover a wide spectrum of patients with any particular cancer requires a large panel of TAA. Currently, two main strategies are used for profiling circulating Ab: (1) conventional serological surveys using phage lysates encoding specific TAA, and (2) ELISA-based approaches using purified recombinant proteins as the antigenic targets. See Stone et al. (2003) Int J Cancer 104:73-84; and Tan et al. (2005) N Engl J Med 353:2815-7. The former approach requires large amounts of sera individually pre-adsorbed with E. coli phage lysates for reduction of background; the latter is a robust method but requires the purification of proteins encoded by individual TAA. See Zhang et al. (2003) Cancer Epidemiol Biomarkers Prev 12:136-43; and Lagarkova et al. (2003) Immunol Lett 85:71-4.